The long-range objectives of the proposed work are to contribute to an understanding of the pathogenesis and immunology of cholera which will lead to rational and effective means of prophylaxis and treatment. As cholera is the prototype of an emerging group of enterotoxic enteropathies, the results should be applicable to other, more common, secretory diarrheal diseases. Our major specific immediate goals are to develop further information on the characteristics and properties of an avirulent mutant of Vibrio cholerae which we have isolated which offers promise as a candidate living vaccine which will colonize the gut and stimulate local immune mechanisms against cholera and related enterotoxic enteropathies; to develop a further understanding of the mechanism(s) by which V. cholerae attaches to intestinal epithelium, which may be pertinent to the pathogenesis and immunology of cholera; to isolate and investigate the properties of a hemolysin from El Tor vibrios and to evaluate further similarities and differences between cholera and other enterotoxins such as the heat-labile enterotoxin (LT) of Escherichia coli.